FDA Approves Takeda-Lundbeck Drug for Major Depressive Disorder

The FDA yesterday approved Brintellix (vortioxetine) for adults with major depressive disorder. The drug, which was co-developed by Takeda Pharmaceutical and H. Lundbeck, is expected to reach the market by year’s end.

Brintellix is an inhibitor of serotonin (5-HT) reuptake, as well as an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors, and an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors. Brintellix is considered the first and only compound with that combination of pharmacodynamic activity, though the companies added that contribution of each of these activities to Brintellix's antidepressant effect has not been established.

That did not stop investigators from establishing the efficacy and safety of Brintellix across a global clinical trial program that included six positive six- to eight-week studies—one of them a dedicated study in elderly patients—that demonstrated statistically significant improvements in overall symptoms of depression. The improvements were measured by the Hamilton Depression Scale (HAMD-24) total score in two short-term studies, including the elderly study, and the Montgomery-Asberg Depression Rating Scale (MADRS) total score in the other studies.

The clinical trial program included a positive 24–64-week, long-term maintenance study in which Brintellix treatment resulted in a statistically significant longer time to recurrence of depressive episodes compared to placebo. Studies evaluated for safety included more than 4,700 patients aged 18 to 88 years.

The most common side-effects reported by participants taking Brintellix in clinical trials included nausea, constipation, and vomiting.

Brintellix will be available in 5 mg, 10 mg, 15 mg, and 20 mg tablets. The World Health Organization has issued a new Anatomical Therapeutic Chemical (ATC) code for Brintellix to be implemented in 2014.

As with other antidepressant drugs, Brintellix will have a boxed warning and a medication guide alerting patients and healthcare professionals that antidepressants can increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults ages 18 to 24 during initial treatment. However, Brintellix itself has not been evaluated for use in pediatric patients.

Brintellix was discovered by Lundbeck researchers in Copenhagen, with Lundbeck and Takeda jointly conducting the drug’s clinical trial program in the United States. Takeda holds the new drug application for the U.S. market under license from Lundbeck.